Cerebrospinal fluid (CSF) cytology is a fundamental test for the diagnosis of central nervous system (CNS) disease in neurological practice in China. CSF cytology provides diagnostic evidence in cases suspected of CNS infectious diseases, autoimmune encephalitis and CNS neoplastic disorders. Immunocytochemistry and flow cytometry make the cytological diagnosis more sensitive and specific. However, the diagnostic significance of CSF cytology should be interpreted and evaluated in the context of specific clinical backgrounds. Although molecular diagnostic techniques, including polymerase chain reaction and next-generation sequencing, are increasingly applied to CSF examination, the classical CSF cytology still has its horizon in the era of precision neurology and should be recommended as a routine test for CSF analysis. Back

Progressive multifocal leukoencephalopathy (PML) is a severe demyelinating disease of the central nervous system caused by the John Cunningham (JC) virus typically seen in immuno-compromised patients. Several drugs that suppress that immune system have already been known to cause PML such as... Read more

Progressive multifocal leukoencephalopathy (PML) is a severe demyelinating disease of the central nervous system caused by the John Cunningham (JC) virus typically seen in immuno-compromised patients. Several drugs that suppress that immune system have already been known to cause PML such as natalizumab and rituximab. We present a patient with sarcoidosis who develops PML in the rare setting of minimal immunosuppression with only hydroxychloroquine. There was significant delay in the diagnosis due to negative cerebrospinal fluid testing for JC virus and concern for neuro-sarcoidosis, but eventually a diagnosis of PML was made via brain biopsy. Back

In recent times, there has been a significant increase in studies focusing on immunological functions of autophagy, however, knowledge of its roles and regulations in the central nervous system remains unclear. Present reviews highlight the molecular cross talk between host cell autophagy with... Read more

In recent times, there has been a significant increase in studies focusing on immunological functions of autophagy, however, knowledge of its roles and regulations in the central nervous system remains unclear. Present reviews highlight the molecular cross talk between host cell autophagy with inflammatory pathways in the context of neuro-infections. Intracellular pathogens might have an ability to manipulate the autophagy regulation process. An augmented autophagy and inflammation at the site of infection is traditionally considered host protective. Moreover, host cell autophagy might also facilitate pathogen survivability and multiplication in the brain environment. Consequently, an excessive autophagy and neuroinflammatory process do put surrounding healthy brain tissue at risk of pathogen invasion. The question arises, whether there are any known direct interactions of intracellular neurotropic pathogens with this degradative pathway that favour intracerebral pathogen survival and growth? It is worth exploring any such cooperation between pathogen factors and altered immune pathways that modulate autophagy regulatory genes causing massive neuronal damage. A detailed understanding of molecular mechanisms in microbial pathogenesis, neuroinflammatory and neuronal autophagy pathways might identify novel therapeutic targets and diagnostic biomarkers. Back

Alzheimer’s disease (AD) is a neurodegenerative disease with proteopathy characterized by abnormalities in amyloid beta (Aβ) and tau proteins. Defective amyloid and tau propagate and aggregate, leading to eventual amyloid plaques and neurofibrillary tangles. New data show that a third... Read more

Alzheimer’s disease (AD) is a neurodegenerative disease with proteopathy characterized by abnormalities in amyloid beta (Aβ) and tau proteins. Defective amyloid and tau propagate and aggregate, leading to eventual amyloid plaques and neurofibrillary tangles. New data show that a third proteopathy, an altered conformation of the scaffolding protein filamin A (FLNA), is critically linked to the amyloid and tau pathologies in AD. Altered FLNA is pervasive in AD brain and without apparent aggregation. In a striking interdependence, altered FLNA is both induced by Aβ and required for two prominent pathogenic signaling pathways of Aβ. Aβ monomers or small oligomers signal via the α7 nicotinic acetylcholine receptor (α7nAChR) to activate kinases that hyperphosphorylate tau to cause neurofibrillary lesions and formation of neurofibrillary tangles. Altered FLNA also enables a persistent activation of toll-like-receptor 4 (TLR4) by Aβ, leading to excessive inflammatory cytokine release and neuroinflammation. The novel AD therapeutic candidate PTI-125 binds and reverses the altered FLNA conformation to prevent Aβ’s signaling via α7nAChR and aberrant activation of TLR4, thus reducing multiple AD-related neuropathologies. As a regulator of Aβ’s signaling via α7nAChR and TLR4, altered FLNA represents a novel AD therapeutic target. Back

Aim: Minocycline has neuroprotective activities in several models of neurological disorders including spinal cord injury (SCI) where it prevents axonal loss and improves functional recovery. There are still gaps of knowledge on minocycline in SCI including whether it ameliorates neuronal loss at... Read more

Aim: Minocycline has neuroprotective activities in several models of neurological disorders including spinal cord injury (SCI) where it prevents axonal loss and improves functional recovery. There are still gaps of knowledge on minocycline in SCI including whether it ameliorates neuronal loss at the focal site of trauma, and whether minocycline reduces the activity of matrix metalloproteinases (MMPs), a family of enzymes implicated in the pathophysiology of SCI. This study addressed these gaps. Methods: Mice were treated with either minocycline or vehicle control after a spinal cord contusion. MMPs were compared between the two groups using real time polymerase chain reaction and zymography. Immunohistochemistry was used to examine microglial activation and neuronal cell death. Results: While several MMP members were elevated in the spinal cord following injury, treatment with minocycline did not affect their expression. Importantly, minocycline reduced the loss of neurons in the epicenter of damage to the spinal cord and in segments caudal and rostral to the injury. Conclusion: Despite the inability of minocycline to alter MMPs, the results of neuroprotection at the lesion site support the continued testing of minocycline as a neuroprotective medication in experimental and clinical SCI. Back

Human sparganosis is a rare disease often affecting muscle, subcutaneous tissue and other locations, but sparganosis invading the brain is rather rare. Cerebral sparganosis has no specific symptoms which makes the diagnosis quite difficult and is usually neglected in the clinic. Here the authors... Read more

Human sparganosis is a rare disease often affecting muscle, subcutaneous tissue and other locations, but sparganosis invading the brain is rather rare. Cerebral sparganosis has no specific symptoms which makes the diagnosis quite difficult and is usually neglected in the clinic. Here the authors reported a case of a 29-year-old female who was diagnosed with cerebral sparganosis and underwent surgery in their department and a brief review of the literature was conducted as well. Back

Aim: A need for Neurologists exists in the US. The majority of Neurology residency graduates go on to additional subspecialty training. Methods: Data from the Accreditation Council for Graduate Medical Education from 2001-2014 and the United Council for Neurologic Subspecialties from was analyzed... Read more

Aim: A need for Neurologists exists in the US. The majority of Neurology residency graduates go on to additional subspecialty training. Methods: Data from the Accreditation Council for Graduate Medical Education from 2001-2014 and the United Council for Neurologic Subspecialties from was analyzed for trends in the number of Neurology subspecialty training programs and their composition. Results: There has been an overall trend of growth in the number of accredited Neurology subspecialty training programs and fellows. These trends vary between specific subspecialties. Conclusion: The authors provide an overview of the contemporary state of Neurology subspecialty training in the US. A clearer understanding of subspecialty training allows for anticipation of workforce surpluses and deficits. Back

Ischemic stroke causes the depletion of energy and induce excitotoxicity and neuroinflammation in the brain that results from thrombotic blockage. Neuroinflammation occurs initially depending on activated resident microglia that has the same function as the macrophage. Activated microglia... Read more

Ischemic stroke causes the depletion of energy and induce excitotoxicity and neuroinflammation in the brain that results from thrombotic blockage. Neuroinflammation occurs initially depending on activated resident microglia that has the same function as the macrophage. Activated microglia participates in the neuroinflammatory process by phagocytosing the injured brain cells and producing the pro- and anti-inflammatory mediators. In this review, the authors present an overview of the role of microglia in mediating neuroinflammation in ischemic stroke. Back

Corpus callosum (CC) is the largest white matter structure in the brain, consisting of 200-250 million contralateral axonal projections. It is the major commissural pathway connecting the hemispheres of human brain. The pathology of CC includes wide variety of entities that arise from different... Read more

Corpus callosum (CC) is the largest white matter structure in the brain, consisting of 200-250 million contralateral axonal projections. It is the major commissural pathway connecting the hemispheres of human brain. The pathology of CC includes wide variety of entities that arise from different causes such as congenital, inflammatory, tumoral, degenerative, infectious, etc. This study reviews the most reliable neuroimaging data of human CC in central nervous system (CNS) demyelinating diseases to facilitate the understanding of different pathological entities of the CC and their role in anticipation of probable prognostic findings. After a brief description of normal anatomy and functions of CC, this review examines the most valuable findings obtained using conventional and functional magnetic resonance imaging. It also demonstrates the most well organized findings of how CC features influence prognostic factors of demyelinating disorders, which could have a great value for choosing proper therapy methods. The authors also provided a brief review of other demyelinating disorders which are primarily caused by other pathological factors other than autoimmunity. As a conclusion, the authors showed the importance of CC as an critical part of the brain, which should be explored by different methods of imaging, correspondent to clinical evaluation of CNS demyelinating disorder to widen our knowledge on pathology and clinical patterns of such disorders. Back

Human cytomegalovirus (HCMV) was reported in glioblastoma multiforme (GBM) over a decade ago and this finding has the potential to increase our understanding of the disease and it offers an alternative tumor-specific therapeutic target. Due of this promise, there is a fair amount of time, energy... Read more

Human cytomegalovirus (HCMV) was reported in glioblastoma multiforme (GBM) over a decade ago and this finding has the potential to increase our understanding of the disease and it offers an alternative tumor-specific therapeutic target. Due of this promise, there is a fair amount of time, energy and money being directed towards understanding and utilizing this connection for eventual therapeutic purposes. Nevertheless, the association between GBM and HCMV remains controversial. Several studies have reported conflicting results, further undermining the potential clinical value of this association. In this review, the authors will discuss the latest developments on this evolving issue. Specifically, the results of the latest studies, both positive and negative, will be discussed. Furthermore, potential theories to explain discrepancies reported in the literature will be proposed. Clinical implications including potential targets for anti-HCMV therapy and the latest developments in anti-HCMV therapy will be presented. Finally, solutions to remedy this controversial issue in neuro-oncology will be offered. Back

Herpes simplex encephalitis (HSE) can cause permanent injury to the brain parenchyma. As such, it is usually treated as a medical emergency for which correct immediate diagnosis and introduction of specific therapies are critical for survival and prognosis. Here, the authors review the current... Read more

Herpes simplex encephalitis (HSE) can cause permanent injury to the brain parenchyma. As such, it is usually treated as a medical emergency for which correct immediate diagnosis and introduction of specific therapies are critical for survival and prognosis. Here, the authors review the current status of diagnosis and treatments and discuss unsolved issues surrounding therapeutic interventions. The authors also highlight the current expectations for future management of HSE. Back

Aim: Minocycline has neuroprotective activities in several models of neurological disorders including spinal cord injury (SCI) where it prevents axonal loss and improves functional recovery. There are still gaps of knowledge on minocycline in SCI including whether it ameliorates neuronal loss at... Read more

Aim: Minocycline has neuroprotective activities in several models of neurological disorders including spinal cord injury (SCI) where it prevents axonal loss and improves functional recovery. There are still gaps of knowledge on minocycline in SCI including whether it ameliorates neuronal loss at the focal site of trauma, and whether minocycline reduces the activity of matrix metalloproteinases (MMPs), a family of enzymes implicated in the pathophysiology of SCI. This study addressed these gaps. Methods: Mice were treated with either minocycline or vehicle control after a spinal cord contusion. MMPs were compared between the two groups using real time polymerase chain reaction and zymography. Immunohistochemistry was used to examine microglial activation and neuronal cell death. Results: While several MMP members were elevated in the spinal cord following injury, treatment with minocycline did not affect their expression. Importantly, minocycline reduced the loss of neurons in the epicenter of damage to the spinal cord and in segments caudal and rostral to the injury. Conclusion: Despite the inability of minocycline to alter MMPs, the results of neuroprotection at the lesion site support the continued testing of minocycline as a neuroprotective medication in experimental and clinical SCI. Back

Aim: Myasthenia gravis (MG) is an autoimmune disease, in which immunotherapy can improve symptoms for a period, but the majority of patients still experience symptomatic fluctuation or develop myasthenic crisis. This study aimed to explore the relationship between frequency of peripheral... Read more

Aim: Myasthenia gravis (MG) is an autoimmune disease, in which immunotherapy can improve symptoms for a period, but the majority of patients still experience symptomatic fluctuation or develop myasthenic crisis. This study aimed to explore the relationship between frequency of peripheral lymphocyte subsets and myasthenia gravis disease stage. Methods: The percentages of B regulatory (Breg) cells and natural killer (NK) cells in the peripheral blood samples obtained from 54 MG patients and 10 healthy controls were surveyed using flow cytometry. MG patients were subdivided into the ocular MG, generalized MG (GMG) in exacerbation stage and GMG in remission stage. Results: The percentage of Breg cells was significantly decreased in both the exacerbation stage (6.93 ± 1.18) and remission stage (6.56 ± 1.32) of GMG patients compared to healthy controls (15.97 ± 2.88). The percentage of NK cells were significantly increased in GMG patients in remission stage (20.69 ± 3.45) compared to healthy controls (11.33 ± 0.95). Frequency of NK cells in the patients in remission stage was significantly increased compared to patients in exacerbation (20.69 ± 3.45 vs. 12.32 ± 1.42). Conclusion: The Breg cells are involved in the pathogenesis of GMG, and NK cells are closely associated with the fluctuation of MG symptoms. NK cells could be a useful marker for MG activity and for monitoring effectiveness of immunotherapy. Back

In recent times, there has been a significant increase in studies focusing on immunological functions of autophagy, however, knowledge of its roles and regulations in the central nervous system remains unclear. Present reviews highlight the molecular cross talk between host cell autophagy with... Read more

In recent times, there has been a significant increase in studies focusing on immunological functions of autophagy, however, knowledge of its roles and regulations in the central nervous system remains unclear. Present reviews highlight the molecular cross talk between host cell autophagy with inflammatory pathways in the context of neuro-infections. Intracellular pathogens might have an ability to manipulate the autophagy regulation process. An augmented autophagy and inflammation at the site of infection is traditionally considered host protective. Moreover, host cell autophagy might also facilitate pathogen survivability and multiplication in the brain environment. Consequently, an excessive autophagy and neuroinflammatory process do put surrounding healthy brain tissue at risk of pathogen invasion. The question arises, whether there are any known direct interactions of intracellular neurotropic pathogens with this degradative pathway that favour intracerebral pathogen survival and growth? It is worth exploring any such cooperation between pathogen factors and altered immune pathways that modulate autophagy regulatory genes causing massive neuronal damage. A detailed understanding of molecular mechanisms in microbial pathogenesis, neuroinflammatory and neuronal autophagy pathways might identify novel therapeutic targets and diagnostic biomarkers. Back

Intracranial lipomas are rare benign tumour that is slow growing, generally asymptomatic, most frequently located in the midline areas and are usually an incidental finding on imaging and therefore cases are not frequently reported. This study reports a case of a patient with quadrigeminal plate... Read more

Intracranial lipomas are rare benign tumour that is slow growing, generally asymptomatic, most frequently located in the midline areas and are usually an incidental finding on imaging and therefore cases are not frequently reported. This study reports a case of a patient with quadrigeminal plate lipoma presenting with obstructive hydrocephalous and the 6th cranial nerve palsy that was successfully treated with ventriculo-peritoneal shunting without addressing the lesion. Back

Injury to the central nervous system (CNS) is common, and though it has been well studied, many aspects of traumatic brain injury (TBI) and stroke are poorly understood. TBI and stroke are two pathologic events that can cause severe, immediate impact to the neurostructure and function of the CNS,... Read more

Injury to the central nervous system (CNS) is common, and though it has been well studied, many aspects of traumatic brain injury (TBI) and stroke are poorly understood. TBI and stroke are two pathologic events that can cause severe, immediate impact to the neurostructure and function of the CNS, which has been recognized recently to be exacerbated by the body’s own immune response. Although the brain damage induced by the initial trauma is most likely unsalvageable, the secondary immunologic deterioration of neural tissue gives ample opportunity for therapeutic strategists seeking to mitigate TBI’s secondary detrimental effects. The purpose of this paper is to highlight the cell death mechanisms associated with CNS injury with special emphasis on inflammation. The authors discuss sources of inflammation, and introduce the role of the spleen in the systemic response to inflammation after CNS injury. Back

Cryptococcal meningitis (CM) is a central nervous system infectious disease caused by Cryptococcus. It is the most common fungal infection in the central nervous system, accounting for about 48% of fungal infection. The disease occurs mainly in acquired immunodeficiency syndrome (AIDS) patients... Read more

Cryptococcal meningitis (CM) is a central nervous system infectious disease caused by Cryptococcus. It is the most common fungal infection in the central nervous system, accounting for about 48% of fungal infection. The disease occurs mainly in acquired immunodeficiency syndrome (AIDS) patients and concentrates in the immunocompromised people without AIDS. There are nearly one million new cases of CM each year, and about 70% of them died. In China, CM occurs mainly in people without AIDS and there is an increasing trend in recent years. Early diagnosis and treatment is the key to reducing morbidity and mortality associated with CM. The diagnosis mainly depends on laboratory examination such as morphological examination, fungal culture and antigen detection. History, clinical manifestation and imaging examination are the important parts of auxiliary examination. The initial combined antifungal treatment is emphasized, and the principle of fractional treatment including induction, consolidation and maintenance therapy should be followed. The high intracranial pressure must be reduced actively at the same time. In addition, it is proved that the novel immunotherapy combined with antifungal agents can improve the curative effect and limit the chance of antimicrobial resistance. Large-scale clinical trials are needed for further study. Back

Fabry disease (FD) is a rare, progressive, multisystem and highly debilitating disease. FD is an X-linked lysosome storage disorder that results in α-galactosidase A deficiency. The subsequent accumulation of glycosphingolipids is more evident in vascular endothelium and smooth-muscle cells. The... Read more

Fabry disease (FD) is a rare, progressive, multisystem and highly debilitating disease. FD is an X-linked lysosome storage disorder that results in α-galactosidase A deficiency. The subsequent accumulation of glycosphingolipids is more evident in vascular endothelium and smooth-muscle cells. The resulting effect of the deposition is generalized inflammation and vasculopathy, which can also affect the central and peripheral nervous system. FD progresses with kidney dysfunction, angiokeratoma of the skin, cardiomyopathy, cerebrovascular events and neurological disorders. In the present review, the neurological manifestations of FD are summarized with emphasis on cerebral vasculopathy, cochlear nerve dysfunction, psychiatric and cognitive symptoms, autonomic dysfunction and peripheral neuropathy. Enzyme replacement therapy is also discussed in the light of its more prominent effects when administered early in life, which make it essential to diagnose FD as soon as possible. Back

Voltage-gated potassium channels (VGKCs) represent a group of tetrameric signaling proteins with several functions, including modulation of neuronal excitability and neurotransmitter release. Moreover, VGKCs give a key contribution to the generation of the action potential. VGKCs are complexed... Read more

Voltage-gated potassium channels (VGKCs) represent a group of tetrameric signaling proteins with several functions, including modulation of neuronal excitability and neurotransmitter release. Moreover, VGKCs give a key contribution to the generation of the action potential. VGKCs are complexed with other neuronal proteins, and it is now widely known that serum autoantibodies directed against VGKCs are actually directed against the potassium channel subunits only in a minority of patients. By contrast, these autoantibodies more commonly target three proteins that are complexed with alpha-dendrotoxin-labeled potassium channels in brain extracts. These three proteins are contactin-associated protein-2 (Caspr-2), leucine-rich, glioma inactivated 1 (LGI-1) protein and the protein Tag-1/contactin-2. Neoplasms are detected only in a minority of seropositive patients for VGKC complex-IgG and do not significantly associate with Caspr-2 or LGI-1. Among all the cancers described in association with VGKC complex-IgG, lung carcinoma, thymoma, and hematologic malignancies are the most commonly detected. We will review all the major neurological conditions associated with VGKC complex-IgG. These include Isaacs' syndrome, Morvan syndrome, limbic encephalitis, facio-brachial dystonic seizures, chorea and other movement disorders, epilepsy, psychosis, gastrointestinal neuromuscular diseases, a subacute encephalopathy that mimics Creutzfeldt-Jakob prion disease both clinically and radiologically and autoimmune chronic pain. The vast majority of these conditions are reversible by immunotherapy, and it is becoming increasingly recognized that early diagnosis and detection of VGKC complex-IgG is critical in order to rapidly start the treatment. As a result, VGKC complex-IgG are now part of the investigation of patients with unexplained subacute onset of epilepsy, memory or cognitive problems, or peripheral nerve hyperexcitability syndromes. Back

Necroptosis is a type of newly identified cell death induced by apoptotic stimuli under conditions where apoptotic execution is prevented. Studies over the past 10 years have revealed the molecular mechanism of necroptosis and challenged the old conception that necrosis is un-programmed.... Read more

Necroptosis is a type of newly identified cell death induced by apoptotic stimuli under conditions where apoptotic execution is prevented. Studies over the past 10 years have revealed the molecular mechanism of necroptosis and challenged the old conception that necrosis is un-programmed. Recently, more and more data have emerged suggesting a close association between necroptosis and inflammation. In this review, the authors summarized the current knowledge of the mechanism of necroptosis, focusing on tumour necrosis factor α induced necroptosis and the roles of necroptosis in regulating inflammation. In particular, we discussed the occurrence of necroptosis and its relation with inflammation in neurological diseases hoping to provide new insight for the research and treatment of neuroinflammatory disorders. Back

Over the past decade the discovery of novel forms of encephalitis associated with neuronal surface antibodies had changed the paradigms for diagnosing and treating disorders that were previously mischaracterized. Recognition of clinical syndromes, consistent methods of diagnosis, and early... Read more

Over the past decade the discovery of novel forms of encephalitis associated with neuronal surface antibodies had changed the paradigms for diagnosing and treating disorders that were previously mischaracterized. Recognition of clinical syndromes, consistent methods of diagnosis, and early targeted immunotherapy can lead to a favorable outcome in diseases that may be associated with significant disability or death if left untreated. Here the conditions associated with neuronal surface antibodies are briefly reviewed, some general aspects of these syndromes are considered and guidelines that could help in the recognition of these disorders are suggested. Furthermore, a diagnostic algorithm to detect and characterize neuronal cell surface autoantibodies is suggested and some of the caveats of serum testing are outlined. Future directions will involve the identification of novel autoantibodies, the standardization of methods to detect and characterize them, as well as evaluation of the most efficacious therapeutic strategies in patients with established diagnosis of autoimmune encephalitis. Back

We present a 41-year-old female with previous history of ependymoma who underwent gross-total resection of the tumor and ventriculo-peritoneal shunt placement, followed by radiotherapy. Three years later a small enhancing area was noted in the left anterolateral spinal cord at the level of the... Read more

We present a 41-year-old female with previous history of ependymoma who underwent gross-total resection of the tumor and ventriculo-peritoneal shunt placement, followed by radiotherapy. Three years later a small enhancing area was noted in the left anterolateral spinal cord at the level of the C1-C2 vertebrae and a left posterior-lateral herniated disk in the C5-C6 level which was not present in the earlier MRI. This is a unique case, in which herniated disk pressuring effects needed to be differentiated from both radiation-induced treatment effect and tumor recurrence. Back

Neuronal surface antibody syndromes (NSAS) encompass a variety of disorders associated with “neuronal surface antibodies”. These share clinical and neuroradiological features that pose challenges related to their recognition and treatment. Recent epidemiological studies show a clear predominance... Read more

Neuronal surface antibody syndromes (NSAS) encompass a variety of disorders associated with “neuronal surface antibodies”. These share clinical and neuroradiological features that pose challenges related to their recognition and treatment. Recent epidemiological studies show a clear predominance for the glutamate-N-methyl-D-aspartate receptor encephalitis in both adults and pediatric population. Despite this, the overall NSAS’s incidence remains underestimated, and diagnosis persists to be not always easy to achieve. Based on current literature data, in this paper the authors propose a diagnostic pathway to approach and treat pediatric NSAS. An autoimmune etiology can be suggested through the integration of clinical, immunological, electrophysiological and neuroradiological data. On that basis, a target treatment can be started, consisting of corticosteroids and intravenous immunoglobulin or plasma exchange as a first-line immunotherapy, followed by second-line drugs including rituximab, cyclophosphamide or mycophenolate mophetil, if the case. In children a prompt diagnosis and a targeted treatment may lead to a better clinical outcome. Nevertheless further studies are required to assess the need of more tailored treatments according to long-term outcome findings and prognostic factors in different NSAS. Back

Amyotrophic lateral sclerosis (ALS) is the most common form of motor neuron disease and is a progressive and devastating neurodegenerative disease that affects both lower and upper motor neurons. Muscle cramps, which are characterized by a sudden, painful, involuntary contraction of muscles, are... Read more

Amyotrophic lateral sclerosis (ALS) is the most common form of motor neuron disease and is a progressive and devastating neurodegenerative disease that affects both lower and upper motor neurons. Muscle cramps, which are characterized by a sudden, painful, involuntary contraction of muscles, are not rare in ALS patients. However, muscle cramps do not normally present early in ALS and therefore not used for the initial diagnosis of ALS. In this paper the authors present a case of ALS with initial manifestation of progressive painful muscle cramps in the absence of muscle weakness. This case might help people to recognize atypical foremost presentations of ALS and therefore formulate effective therapies. Back

Aim: A need for Neurologists exists in the US. The majority of Neurology residency graduates go on to additional subspecialty training. Methods: Data from the Accreditation Council for Graduate Medical Education from 2001-2014 and the United Council for Neurologic Subspecialties from was analyzed... Read more

Aim: A need for Neurologists exists in the US. The majority of Neurology residency graduates go on to additional subspecialty training. Methods: Data from the Accreditation Council for Graduate Medical Education from 2001-2014 and the United Council for Neurologic Subspecialties from was analyzed for trends in the number of Neurology subspecialty training programs and their composition. Results: There has been an overall trend of growth in the number of accredited Neurology subspecialty training programs and fellows. These trends vary between specific subspecialties. Conclusion: The authors provide an overview of the contemporary state of Neurology subspecialty training in the US. A clearer understanding of subspecialty training allows for anticipation of workforce surpluses and deficits. Back

The standard treatment of glioblastoma, the most common type of primary-brain-tumor, involves radiotherapy with concomitant temozolomide chemotherapy. A patient with glioblastoma, post radiotherapy developed magnatic resonance imaging (MRI) changes consistent with either radiation-induced tumor... Read more

The standard treatment of glioblastoma, the most common type of primary-brain-tumor, involves radiotherapy with concomitant temozolomide chemotherapy. A patient with glioblastoma, post radiotherapy developed magnatic resonance imaging (MRI) changes consistent with either radiation-induced tumor necrosis or tumor recurrence. Perfusion MRI was suggestive of radiation necrosis, but magnetic resonance spectroscopy and 99mTc-Tetrofosmin single photon emission computed tomography was indicative of tumor recurrence. Positron emission tomography scan was not available. Tumor recurrence was documented by biopsy. Several advanced imaging methods are available to differentiate tumor recurrence from radiation necrosis in glioblastoma patients. However, in inconclusive cases, brain biopsy should be performed for definite diagnosis. Back

Aim: The aim was to investigate the infectious conditions of Epstein-Barr virus (EBV) in patients with multiple sclerosis (MS). Methods: Cerebrospinal fluid (CSF) of 20 patients with MS and 20 with other neurological diseases (OND) were tested with indirect immunofluorescence for anti-EBV capsid... Read more

Aim: The aim was to investigate the infectious conditions of Epstein-Barr virus (EBV) in patients with multiple sclerosis (MS). Methods: Cerebrospinal fluid (CSF) of 20 patients with MS and 20 with other neurological diseases (OND) were tested with indirect immunofluorescence for anti-EBV capsid antigen (EBV-CA) immunoglobulin G (IgG), IgG affinity for anti-EBV-CA, anti-EBV-CA immunoglobulin M (IgM), anti-EBV early antigen (EBV-EA) IgG and anti-EBV nuclear antigen (EBNA) IgG. According to the pattern of antibodies in CSF, infection rates of acute, chronic, primary, recurrent, and past infections were analyzed in the two groups of patients. Results: There were no significant differences in anti-EBV-CA, anti-EBC-EA, and anti-EBNA antigen IgG in CSF between MS and OND patients (P > 0.05). The positive rate of low affinity for anti-EBV-CA IgG in MS patients was significantly higher than that for OND patients (75% vs. 40%, P < 0.05). Furthermore, significant differences in the positive rate of anti-EBV-CA IgM were found between MS and OND patients (70% vs. 25%, P<0.05). Of the MS patients, 75% were in an EBV acute infection state compared with 40% of OND patients (P < 0.05). Conclusion: Acute infection of EBV closely correlates with the occurrence of MS. Back

Fabry disease (FD) is a rare, progressive, multisystem and highly debilitating disease. FD is an X-linked lysosome storage disorder that results in α-galactosidase A deficiency. The subsequent accumulation of glycosphingolipids is more evident in vascular endothelium and smooth-muscle cells. The... Read more

Fabry disease (FD) is a rare, progressive, multisystem and highly debilitating disease. FD is an X-linked lysosome storage disorder that results in α-galactosidase A deficiency. The subsequent accumulation of glycosphingolipids is more evident in vascular endothelium and smooth-muscle cells. The resulting effect of the deposition is generalized inflammation and vasculopathy, which can also affect the central and peripheral nervous system. FD progresses with kidney dysfunction, angiokeratoma of the skin, cardiomyopathy, cerebrovascular events and neurological disorders. In the present review, the neurological manifestations of FD are summarized with emphasis on cerebral vasculopathy, cochlear nerve dysfunction, psychiatric and cognitive symptoms, autonomic dysfunction and peripheral neuropathy. Enzyme replacement therapy is also discussed in the light of its more prominent effects when administered early in life, which make it essential to diagnose FD as soon as possible. Back

Acquired isolated palatal palsy is a rare disease. It is commonly seen in children. It usually presents with acute onset nasal regurgitation of fluids, rhinolalia, and palatal asymmetry. Many causes of this disease, such as infections, trauma, tumor, and brainstem lesions, etc., have been... Read more

Acquired isolated palatal palsy is a rare disease. It is commonly seen in children. It usually presents with acute onset nasal regurgitation of fluids, rhinolalia, and palatal asymmetry. Many causes of this disease, such as infections, trauma, tumor, and brainstem lesions, etc., have been reported. However, the most plausible explanation is immunological/ischemic damage to the affected nerve. After ruling out major potential causes of this disease, the damage is often considered to be idiopathic in nature. This disease has a benign self‑limiting course with excellent recovery. In accordance with a hypothesized immunological basis for this condition, treatment with steroids results in significant improvement in its clinical features. Back

Myasthenia gravis (MG) is an acquired autoimmune disease affecting synaptic transmission via the neuromuscular junction mainly due to the presence of auto-antibodies targeting acetylcholine receptors. Ocular or generalized MG is clinically diagnosed when the extra-ocular muscles or other muscle... Read more

Myasthenia gravis (MG) is an acquired autoimmune disease affecting synaptic transmission via the neuromuscular junction mainly due to the presence of auto-antibodies targeting acetylcholine receptors. Ocular or generalized MG is clinically diagnosed when the extra-ocular muscles or other muscle groups beyond the extra-ocular muscles are involved. MG occurs in both sexes at any ages from all races but shows a wide variability in incidence and prevalence. Differences in clinical phenotypes of MG patients between West and East countries have been observed. Herein, we review the current concept on epidemiology, classification, and generalized progression in MG, mainly focusing on the differential features from mainland China. Back

Over the past decade the discovery of novel forms of encephalitis associated with neuronal surface antibodies had changed the paradigms for diagnosing and treating disorders that were previously mischaracterized. Recognition of clinical syndromes, consistent methods of diagnosis, and early... Read more

Over the past decade the discovery of novel forms of encephalitis associated with neuronal surface antibodies had changed the paradigms for diagnosing and treating disorders that were previously mischaracterized. Recognition of clinical syndromes, consistent methods of diagnosis, and early targeted immunotherapy can lead to a favorable outcome in diseases that may be associated with significant disability or death if left untreated. Here the conditions associated with neuronal surface antibodies are briefly reviewed, some general aspects of these syndromes are considered and guidelines that could help in the recognition of these disorders are suggested. Furthermore, a diagnostic algorithm to detect and characterize neuronal cell surface autoantibodies is suggested and some of the caveats of serum testing are outlined. Future directions will involve the identification of novel autoantibodies, the standardization of methods to detect and characterize them, as well as evaluation of the most efficacious therapeutic strategies in patients with established diagnosis of autoimmune encephalitis. Back

Neuronal surface antibody syndromes (NSAS) encompass a variety of disorders associated with “neuronal surface antibodies”. These share clinical and neuroradiological features that pose challenges related to their recognition and treatment. Recent epidemiological studies show a clear predominance... Read more

Neuronal surface antibody syndromes (NSAS) encompass a variety of disorders associated with “neuronal surface antibodies”. These share clinical and neuroradiological features that pose challenges related to their recognition and treatment. Recent epidemiological studies show a clear predominance for the glutamate-N-methyl-D-aspartate receptor encephalitis in both adults and pediatric population. Despite this, the overall NSAS’s incidence remains underestimated, and diagnosis persists to be not always easy to achieve. Based on current literature data, in this paper the authors propose a diagnostic pathway to approach and treat pediatric NSAS. An autoimmune etiology can be suggested through the integration of clinical, immunological, electrophysiological and neuroradiological data. On that basis, a target treatment can be started, consisting of corticosteroids and intravenous immunoglobulin or plasma exchange as a first-line immunotherapy, followed by second-line drugs including rituximab, cyclophosphamide or mycophenolate mophetil, if the case. In children a prompt diagnosis and a targeted treatment may lead to a better clinical outcome. Nevertheless further studies are required to assess the need of more tailored treatments according to long-term outcome findings and prognostic factors in different NSAS. Back

This review examines glioma disease initiation, promotion, and progression with a focus on the cell types present within the tumor mass and the molecules responsible for the immunosuppressive microenvironment that are present at each step of the disease. The cell types and molecules present also... Read more

This review examines glioma disease initiation, promotion, and progression with a focus on the cell types present within the tumor mass and the molecules responsible for the immunosuppressive microenvironment that are present at each step of the disease. The cell types and molecules present also correlate with the grade of malignancy. An overall "type 2" chronic inflammatory microenvironment develops that facilitates glioma promotion and contributes to the neo-vascularization characteristic of gliomas. An immunosuppressive microenvironment shields the tumor mass from clearance by the patient's own immune system. Here, we provide suggestions to deal with a chronically-inflamed tumor microenvironment and provide recommendations to help optimize adjuvant immune- and gene therapies currently offered to glioma patients. Back

Aim: The aim was to validate a newly developed methodology of semi-automatic image analysis to analyze microglial morphology as marker for microglial activation in ionized calcium-binding adaptor protein-1 (IBA-1) stained brain sections. Methods: The novel method was compared to currently used... Read more

Aim: The aim was to validate a newly developed methodology of semi-automatic image analysis to analyze microglial morphology as marker for microglial activation in ionized calcium-binding adaptor protein-1 (IBA-1) stained brain sections. Methods: The novel method was compared to currently used analysis methods, visual characterization of activation stage and optical density measurement, in brain sections of young and aged rats that had undergone surgery or remained naοve. Results: The cell body to cell size ratio of microglia was strongly correlated to the visual characterization activation stage. In addition, we observed specific surgery and age-related changes in cell body size, size of the dendritic processes and cell body to cell size ratio. Conclusion: The novel analysis method provides a sensitive marker for microglial activation in the rat brain, which is quick and easy to perform and provides additional information about microglial morphology. Back

Necroptosis is a type of newly identified cell death induced by apoptotic stimuli under conditions where apoptotic execution is prevented. Studies over the past 10 years have revealed the molecular mechanism of necroptosis and challenged the old conception that necrosis is un-programmed.... Read more

Necroptosis is a type of newly identified cell death induced by apoptotic stimuli under conditions where apoptotic execution is prevented. Studies over the past 10 years have revealed the molecular mechanism of necroptosis and challenged the old conception that necrosis is un-programmed. Recently, more and more data have emerged suggesting a close association between necroptosis and inflammation. In this review, the authors summarized the current knowledge of the mechanism of necroptosis, focusing on tumour necrosis factor α induced necroptosis and the roles of necroptosis in regulating inflammation. In particular, we discussed the occurrence of necroptosis and its relation with inflammation in neurological diseases hoping to provide new insight for the research and treatment of neuroinflammatory disorders. Back